Article
Discovery of (E)-N-(4-methyl-5-(3-(2-(pyridin-2-yl)vinyl)-1H-indazol-6-yl)thiazol-2-yl)-2-(4-methylpiperazin-1-yl)acetamide (IHMT-TRK-284) as a novel orally available type II TRK kinase inhibitor capable of overcoming multiple resistant mutants.
European journal of medicinal chemistry - 1 Dec 2020
Wang Beilei, Zhang Wentao, Liu Xuesong, Zou Fengming, Wang Junjie, Liu Qingwang, Wang Aoli, Hu Zhenquan, Chen Yongfei, Qi Shuang, Jiang Zongru, Chen Cheng, Hu Chen, Wang Li, Wang Wenchao, Liu Qingsong, Liu Jing
Abstract excerpt
Due to the critical tumorigenic role of fused NTRK genes in multiple cancers, TRK kinases have attracted extensive attention as a drug discovery target. Starting from an indazole based scaffold, through the type II kinase inhibitor fragments hybrid design approach with a ring closure strategy, we discovered a novel potent type II TRK kinase inhibitor compound 34 (IHMT-TRK-284), which exhibited IC50 values of...
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